98th Annual Meeting DOG 2000

P 77

Pharmocokinetics of a new Fluorescein-Lyphilisate in human eyes – a fluorophotometric study

S. Dinslage1, A. Weichselbaum2, R. Süverkrüp2, M. Diestelhorst1, G. K. Krieglstein1

Purpose: To assess the ocular bioavailability of fluorescein from a novel water-free freeze dried ophthalmic drug delivery system compared to conventional eyedrops.

Methods: Fluorescein was dissolved in a 1,0% aqueous solution of hydroxypropylmethyl cellulose (HPMC, Methocel™ E50), filtered, deposited on sterilized flexible hydrophobic polytetrafluoroethylene (PTFE) carrier strips and freeze-dried under aseptic conditions. The fluorescein dose of the lyophilisate was 68 ug corresponding to a conventional drop of Fluorescein SE Thilo®. In a randomized open label study 12 healthy volunteers applied the lyophilizied fluorescein to one eye and conventional fluorescein eye drop to the fellow eye. Fluorophotometric measurements of fluorescein concentrations in the anterior segment were performed with the Fluotron Master™ (Ocumetrics, USA) before, +15,+30,+45,+60,+120 and +180 minutes after application. The fluorescein concentration of corneal stroma (CS), mid anterior chamber (AC) and the area under the curve (AUC) from cornea peak to anterior lens surface were compared and analyzed by one way ANOVA.

Results: AUC, CS and AC mean values were higher in the eyes treated with the new lyophilisate during the whole time curve. The AUC showed a significant fluorescein increase at 15 and 180 minutes, CS at 15,45,60,180 minutes and all AC concentrations over time after application (p<0.05). The fluorescein uptake of the lyophilisate treated eyes was up to 34 times higher compared to conventional eyedrops.

Conclusions: Lyophilized eyedrops are a favourable alternative to conventional eyedrops with many advantages like depot effect, easy to use, less eye injuries, free of preservatives and chemical stability. The better pharmacokinetic is due to a water-free application where no volume drains the nasolacrimal duct.

1Dept. of Ophthalmology, University of Cologne, Germany
Dept. of Pharmaceutical Technology, University of Bonn, Germany